Blogs

CRISPR & FSHD

April 26, 2016

Harnessing a New Technology

CRISPR is a technology that researchers have been embracing with enthusiasm all over the world. Our recent article Altering Gene Expression gives a brief overview of what CRISPR is and how it works. Essentially CRISPR is a way of making targeted changes in the genome or modulating the expression of specific genes and it is being investigated for many biomedical applications. Here we look at the first study using CRISPR in FSHD.

FSHD is an unusually complex disease. The genetic variant thought to be responsible for the condition was described in the early 1990s and the gene DUX4 named as the key culprit. The DUX4 protein activates a host of genes not normally expressed in muscle cells, leading to pathology. In people without FSHD the region of the genome where DUX4 is located is silent. The DNA is wrapped tightly and no genes are being expressed. In FSHD patients, the opposite is true. Recently the Jones laboratory at the University of Massachusetts Medical School published results from their own experiments using CRISPR.(1) In their study they were investigating whether it was possible to use the CRISPR technology to put this area of the genome back to sleep in people with FSHD.

Using a variant of the standard CRISPR tool, the researchers were able to repress DUX4 expression in muscle cells with the FSHD defect. The results from their study showed that CRISPR was able to target the defective genomic region, repress DUX4 expression, and decrease the expression of DUX4 target genes.
This work is an exciting step for treatments that specifically target the genetic defect in FSHD. “Our work represents an important first step towards therapy for FSHD,” said Peter Jones, “and we are continuing to aggressively pursue CRISPR-based applications for FSHD in the hopes of eventually reaching the clinic.”

1. Himeda CL, Jones TI, Jones PL. CRISPR/dCas9-mediated Transcriptional Inhibition Ameliorates the Epigenetic Dysregulation at D4Z4 and Represses DUX4-fl in FSH Muscular Dystrophy. Molecular therapy : the journal of the American Society of Gene Therapy. 2016;24(3):527-35.